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P80075

- CCL8_HUMAN

UniProt

P80075 - CCL8_HUMAN

Protein

C-C motif chemokine 8

Gene

CCL8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils. May play a role in neoplasia and inflammatory host responses. This protein can bind heparin. The processed form MCP-2(6-76) does not show monocyte chemotactic activity, but inhibits the chemotactic effect most predominantly of CCL7, and also of CCL2 and CCL5 and CCL8.1 Publication

    GO - Molecular functioni

    1. chemokine activity Source: ProtInc
    2. heparin binding Source: UniProtKB-KW
    3. phospholipase activator activity Source: UniProtKB
    4. protein kinase activity Source: UniProtKB

    GO - Biological processi

    1. calcium ion transport Source: UniProtKB
    2. cell-cell signaling Source: UniProtKB
    3. cell chemotaxis Source: GOC
    4. cellular calcium ion homeostasis Source: UniProtKB
    5. chemotaxis Source: ProtInc
    6. exocytosis Source: UniProtKB
    7. immune response Source: InterPro
    8. inflammatory response Source: UniProtKB-KW
    9. positive regulation of catalytic activity Source: GOC
    10. protein phosphorylation Source: GOC
    11. response to virus Source: ProtInc
    12. signal transduction Source: ProtInc

    Keywords - Molecular functioni

    Cytokine

    Keywords - Biological processi

    Chemotaxis, Inflammatory response

    Keywords - Ligandi

    Heparin-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    C-C motif chemokine 8
    Alternative name(s):
    HC14
    Monocyte chemoattractant protein 2
    Monocyte chemotactic protein 2
    Short name:
    MCP-2
    Small-inducible cytokine A8
    Cleaved into the following chain:
    Gene namesi
    Name:CCL8
    Synonyms:MCP2, SCYA10, SCYA8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:10635. CCL8.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular space Source: UniProtKB-KW

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA35567.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323CuratedAdd
    BLAST
    Chaini24 – 9976C-C motif chemokine 8PRO_0000005188Add
    BLAST
    Chaini29 – 9971MCP-2(6-76)PRO_0000005189Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei24 – 241Pyrrolidone carboxylic acid1 Publication
    Disulfide bondi34 ↔ 591 Publication
    Disulfide bondi35 ↔ 751 Publication

    Post-translational modificationi

    N-terminal processed form MCP-2(6-76) is produced by proteolytic cleavage after secretion from peripheral blood monocytes.1 Publication

    Keywords - PTMi

    Disulfide bond, Pyrrolidone carboxylic acid

    Proteomic databases

    PaxDbiP80075.
    PRIDEiP80075.

    Miscellaneous databases

    PMAP-CutDBP80075.

    Expressioni

    Tissue specificityi

    Highest expression found in the small intestine and peripheral blood cells. Intermediate levels seen in the heart, placenta, lung, skeletal muscle, thymus, colon, ovary, spinal cord and pancreas. Low levels seen in the brain, liver, spleen and prostate.

    Inductioni

    By IFNG/IFN-gamma, mitogens and IL1/interleukin-1.

    Gene expression databases

    ArrayExpressiP80075.
    BgeeiP80075.
    CleanExiHS_CCL8.
    GenevestigatoriP80075.

    Interactioni

    Subunit structurei

    Monomer or homodimer; in equilibrium.1 Publication

    Protein-protein interaction databases

    BioGridi112258. 2 interactions.
    DIPiDIP-5871N.
    MINTiMINT-103111.
    STRINGi9606.ENSP00000225840.

    Structurei

    Secondary structure

    1
    99
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni26 – 294
    Helixi45 – 473
    Beta strandi48 – 536
    Beta strandi59 – 613
    Beta strandi64 – 685
    Beta strandi73 – 764
    Helixi81 – 9616

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ESRX-ray2.00A24-99[»]
    ProteinModelPortaliP80075.
    SMRiP80075. Positions 24-99.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP80075.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG75507.
    HOGENOMiHOG000036686.
    HOVERGENiHBG017871.
    InParanoidiP80075.
    KOiK16596.
    OMAiQKLESYT.
    OrthoDBiEOG7C5MC2.
    PhylomeDBiP80075.
    TreeFamiTF334888.

    Family and domain databases

    InterProiIPR000827. Chemokine_CC_CS.
    IPR001811. Chemokine_IL8-like_dom.
    [Graphical view]
    PfamiPF00048. IL8. 1 hit.
    [Graphical view]
    SMARTiSM00199. SCY. 1 hit.
    [Graphical view]
    SUPFAMiSSF54117. SSF54117. 1 hit.
    PROSITEiPS00472. SMALL_CYTOKINES_CC. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P80075-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKVSAALLCL LLMAATFSPQ GLAQPDSVSI PITCCFNVIN RKIPIQRLES   50
    YTRITNIQCP KEAVIFKTKR GKEVCADPKE RWVRDSMKHL DQIFQNLKP 99
    Length:99
    Mass (Da):11,246
    Last modified:November 1, 1997 - v2
    Checksum:i9D67976BB9422F2A
    GO

    Sequence cautioni

    The sequence CAA68168.1 differs from that shown. Reason: Erroneous initiation.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti14 – 141A → V.
    Corresponds to variant rs35401229 [ dbSNP | Ensembl ].
    VAR_048704
    Natural varianti69 – 691K → Q.3 Publications
    Corresponds to variant rs1133763 [ dbSNP | Ensembl ].
    VAR_001633

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X99886 Genomic DNA. Translation: CAA68168.1. Different initiation.
    Y10802 mRNA. Translation: CAA71760.1.
    Y16645 mRNA. Translation: CAA76341.1.
    BC126242 mRNA. Translation: AAI26243.1.
    CCDSiCCDS11280.1.
    PIRiJC5295.
    RefSeqiNP_005614.2. NM_005623.2.
    UniGeneiHs.271387.

    Genome annotation databases

    EnsembliENST00000394620; ENSP00000378118; ENSG00000108700.
    GeneIDi6355.
    KEGGihsa:6355.
    UCSCiuc002hib.3. human.

    Polymorphism databases

    DMDMi2506280.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    CCL8 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X99886 Genomic DNA. Translation: CAA68168.1 . Different initiation.
    Y10802 mRNA. Translation: CAA71760.1 .
    Y16645 mRNA. Translation: CAA76341.1 .
    BC126242 mRNA. Translation: AAI26243.1 .
    CCDSi CCDS11280.1.
    PIRi JC5295.
    RefSeqi NP_005614.2. NM_005623.2.
    UniGenei Hs.271387.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1ESR X-ray 2.00 A 24-99 [» ]
    ProteinModelPortali P80075.
    SMRi P80075. Positions 24-99.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112258. 2 interactions.
    DIPi DIP-5871N.
    MINTi MINT-103111.
    STRINGi 9606.ENSP00000225840.

    Polymorphism databases

    DMDMi 2506280.

    Proteomic databases

    PaxDbi P80075.
    PRIDEi P80075.

    Protocols and materials databases

    DNASUi 6355.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000394620 ; ENSP00000378118 ; ENSG00000108700 .
    GeneIDi 6355.
    KEGGi hsa:6355.
    UCSCi uc002hib.3. human.

    Organism-specific databases

    CTDi 6355.
    GeneCardsi GC17P032646.
    HGNCi HGNC:10635. CCL8.
    MIMi 602283. gene.
    neXtProti NX_P80075.
    PharmGKBi PA35567.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG75507.
    HOGENOMi HOG000036686.
    HOVERGENi HBG017871.
    InParanoidi P80075.
    KOi K16596.
    OMAi QKLESYT.
    OrthoDBi EOG7C5MC2.
    PhylomeDBi P80075.
    TreeFami TF334888.

    Miscellaneous databases

    ChiTaRSi CCL8. human.
    EvolutionaryTracei P80075.
    GeneWikii CCL8.
    GenomeRNAii 6355.
    NextBioi 24684.
    PMAP-CutDB P80075.
    PROi P80075.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P80075.
    Bgeei P80075.
    CleanExi HS_CCL8.
    Genevestigatori P80075.

    Family and domain databases

    InterProi IPR000827. Chemokine_CC_CS.
    IPR001811. Chemokine_IL8-like_dom.
    [Graphical view ]
    Pfami PF00048. IL8. 1 hit.
    [Graphical view ]
    SMARTi SM00199. SCY. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54117. SSF54117. 1 hit.
    PROSITEi PS00472. SMALL_CYTOKINES_CC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2."
      van Coillie E., Fiten P., Nomiyama H., Sakaki Y., Miura R., Yoshie O., van Damme J., Opdenakker G.
      Genomics 40:323-331(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-69.
    2. "Human monocyte chemotactic protein-2: cDNA cloning and regulated expression of mRNA in mesenchymal cells."
      van Coillie E., Froyen F., Nomiyama H., Miura R., Fiten P., van Aelst I., van Damme J., Opdenakker G.
      Biochem. Biophys. Res. Commun. 231:726-730(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-69.
      Tissue: Bone marrow.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-69.
    4. "Cloning and expression of a gamma-interferon-inducible gene in monocytes: a new member of a cytokine gene family."
      Chang H.C., Hsu F., Freeman G.J., Griffin J.D., Reinherz E.L.
      Int. Immunol. 1:388-397(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-99.
    5. "Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family."
      van Damme J., Proost P., Lenaerts J.-P., Opdenakker G.
      J. Exp. Med. 176:59-65(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 26-99.
      Tissue: Osteosarcoma.
    6. "Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3."
      Kim K.-S., Rajarathnam K., Clark-Lewis I., Sykes B.D.
      FEBS Lett. 395:277-282(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT.
    7. "Posttranslational modifications affect the activity of the human monocyte chemotactic proteins MCP-1 and MCP-2: identification of MCP-2(6-76) as a natural chemokine inhibitor."
      Proost P., Struyf S., Couvreur M., Lenaerts J.-P., Conings R., Menten P., Verhaert P., Wuyts A., Van Damme J.
      J. Immunol. 160:4034-4041(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION OF MCP-2(6-76), IDENTIFICATION BY MASS SPECTROMETRY, PROTEOLYTIC PROCESSING OF N-TERMINAL, FUNCTION.
    8. "Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors."
      Blaszczyk J., Coillie E.V., Proost P., Damme J.V., Opdenakker G., Bujacz G.D., Wang J.M., Ji X.
      Biochemistry 39:14075-14081(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-99, PYROGLUTAMATE FORMATION AT GLN-24, DISULFIDE BONDS.

    Entry informationi

    Entry nameiCCL8_HUMAN
    AccessioniPrimary (citable) accession number: P80075
    Secondary accession number(s): A0AV77, P78388
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: November 1, 1997
    Last modified: October 1, 2014
    This is version 145 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3